MIRIAM VERONICA FLOR PARK
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
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- How Ancestry Influences the Chances of Finding Unrelated Donors: An Investigation in Admixed Brazilians(2020) NUNES, Kelly; AGUIAR, Vitor R. C.; SILVA, Marcio; SENA, Alexandre C.; OLIVEIRA, Danielli C. M. de; DINARDO, Carla L.; KEHDY, Fernanda S. G.; TARAZONA-SANTOS, Eduardo; ROCHA, Vanderson G.; CARNEIRO-PROIETTI, Anna Barbara F.; LOUREIRO, Paula; FLOR-PARK, Miriam V.; MAXIMO, Claudia; KELLY, Shannon; CUSTER, Brian; WEIR, Bruce S.; SABINO, Ester C.; PORTO, Luis Cristovao; MEYER, DiogoA match of HLA loci between patients and donors is critical for successful hematopoietic stem cell transplantation. However, the extreme polymorphism of HLA loci - an outcome of millions of years of natural selection - reduces the chances that two individuals will carry identical combinations of multilocus HLA genotypes. Further, HLA variability is not homogeneously distributed throughout the world: African populations on average have greater variability than non-Africans, reducing the chances that two unrelated African individuals are HLA identical. Here, we explore how self-identification (often equated with ""ethnicity"" or ""race"") and genetic ancestry are related to the chances of finding HLA compatible donors in a large sample from Brazil, a highly admixed country. We query REDOME, Brazil's Bone Marrow Registry, and investigate how different criteria for identifying ancestry influence the chances of finding a match. We find that individuals who self-identify as ""Black"" and ""Mixed"" on average have lower chances of finding matches than those who self-identify as ""White"" (up to 57% reduction). We next show that an individual's African genetic ancestry, estimated using molecular markers and quantified as the proportion of an individual's genome that traces its ancestry to Africa, is strongly associated with reduced chances of finding a match (up to 60% reduction). Finally, we document that the strongest reduction in chances of finding a match is associated with having an MHC region of exclusively African ancestry (up to 75% reduction). We apply our findings to a specific condition, for which there is a clinical indication for transplantation: sickle-cell disease. We show that the increased African ancestry in patients with this disease leads to reduced chances of finding a match, when compared to the remainder of the sample, without the condition. Our results underscore the influence of ancestry on chances of finding compatible HLA matches, and indicate that efforts guided to increasing the African component of registries are necessary.
- Prevalence of serologic markers of transfusion and sexually transmitted infections and their correlation with clinical features in a large cohort of Brazilian patients with sickle cell disease(2020) BLATYTA, Paula F.; KELLY, Shannon; SABINO, Ester; PREISS, Liliana; MENDES, Franciane; CARNEIRO-PROIETTI, Anna B.; RODRIGUES, Daniela de Oliveira Werneck; MOTA, Rosimere; LOUREIRO, Paula; MAXIMO, Claudia; PARK, Miriam; MENDRONE-JR, Alfredo; GONCALEZ, Thelma T.; ALMEIDA NETO, Cesar de; CUSTER, BrianBACKGROUND: Patients with sickle cell disease (SCD) often require red blood cell (RBC) transfusion for clinical complications, so may be exposed to transfusion-transmitted infections (TTIs). The prevalence of markers for human immunodeficiency virus (HIV), hepatitis C virus (HCV) and B (HBV), human T-cell lymphotropic virus (HTLV-1/2), Chagas disease, and syphilis in an SCD cohort in Brazil were studied. STUDY DESIGN AND METHODS: Clinical history, interview data, blood samples, and medical chart review data were collected during cohort enrollment from November 2013 to May 2015. Serologic markers of infection were assessed. Standard measures of statistical association were calculated, and multivariable models were developed for the most prevalent infections to identify associated factors. RESULTS: Infectionmarkers were evident in 5.2% (144/2779) of the enrolled cohort. Anti-HCV was detected in 69 (2.5%), syphilis antibodies in 34 (1.2%), anti-HTLV-1/2 in 17 (0.6%), HBV surface antigen in 13 (0.5%), Chagas disease antibodies in 13 (0.5%), and anti-HIV in 8 (0.3%) of participants. Factors associated with increased odds of being anti-HCV reactive were older age, illegal drug use, increasing number of RBCs, more than three pain crises in the previous year, and geographic location. Syphilis was associated with older age, females, and smoking history. CONCLUSION: HCV infection was more common in older patients who may have received RBCs before testing was performed on donations, suggesting possible historic transfusion transmission. The cohort showed decreasing rates of infections and a reduction in transfusion transmission markers in younger patients compared to historical literature except for syphilis, indicating contemporary reduced risk of TTI.
- The Sickle Cell Disease Ontology: Enabling Collaborative Research and Co-Designing of New Planetary Health Applications(2020) NEMBAWARE, Victoria; MAZANDU, Gaston K.; HOTCHKISS, Jade; SERUFURI, Jean-Michel Safari; KENT, Jill; KENGNE, Andre Pascal; ANIE, Kofi; MUNUNG, Nchangwi Syntia; BUKINI, Daima; BITOUNGUI, Valentina Josiane Ngo; MUNUBE, Deogratias; CHIRWA, Uzima; CHUNDA-LIYOKA, Catherine; JONATHAN, Agnes; FLOR-PARK, Miriam V.; ESOH, Kevin Kum; JONAS, Mario; MNIKA, Khuthala; OOSTERWYK, Chandre; MASAMU, Upendo; MORRICE, Jack; UWINEZA, Annette; NGUWENEZA, Arthemon; BANDA, Kambe; NYANOR, Isaac; ADJEI, David Nana; SIEBU, Nathan Edward; NKANYEMKA, Malula; KUONA, Patience; TAYO, Bamidele O.; CAMPBELL, Andrew; ORON, Assaf P.; NNODU, Obiageli E.; PAINSTIL, Vivian; MAKANI, Julie; MULDER, Nicola; WONKAM, AmbroiseSickle cell disease (SCD) is one of the most common blood disorders impacting planetary health. Over 300,000 newborns are diagnosed with SCD each year globally, with an increasing trend. The sickle cell disease ontology (SCDO) is the most comprehensive multidisciplinary SCD knowledge portal. The SCDO was collaboratively developed by the SCDO working group, which includes experts in SCD and data standards from across the globe. This expert review presents highlights and lessons learned from the fourth SCDO workshop that marked the beginning of applications toward planetary health impact, and with an eye to empower and cultivate multisite SCD collaborative research. The workshop was organized by the Sickle Africa Data Coordinating Center (SADaCC) and attended by 44 participants from 14 countries, with 2 participants connecting remotely. Notably, from the standpoint of democratizing and innovating scientific meeting design, an SCD patient advocate also presented at the workshop, giving a broader real-life perspective on patients' aspirations, needs, and challenges. A major component of the workshop was new approaches to harness SCDO to harmonize data elements used by different studies. This was facilitated by a web-based platform onto which participants uploaded data elements from previous or ongoing SCD-relevant research studies before the workshop, making multisite collaborative research studies based on existing SCD data possible, including multisite cohort, SCD global clinical trials, and SCD community engagement approaches. Trainees presented proposals for systematic literature reviews in key SCD research areas. This expert review emphasizes potential and prospects of SCDO-enabled data standards and harmonization to facilitate large-scale global SCD collaborative initiatives. As the fields of public and global health continue to broaden toward planetary health, the SCDO is well poised to play a prominent role to decipher SCD pathophysiology further, and co-design diagnostics and therapeutics innovation in the field.
- Blood utilization and characteristics of patients treated with chronic transfusion therapy in a large cohort of Brazilian patients with sickle cell disease(2020) KELLY, Shannon; BELISARIO, Andre Rolim; RODRIGUES, Daniela O. Werneck; CARNEIRO-PROIETTI, Anna B. F.; GONCALEZ, Thelma T.; LOUREIRO, Paula; V, Miriam Flor-Park; MAXIMO, Claudia; MOTA, Rosimere Afonso; DINARDO, Carla; BRAMBILLA, Don; PREISS, Liliana; SABINO, Ester; CUSTER, BrianBACKGROUND Red blood cell (RBC) transfusions are used in sickle cell disease (SCD) to treat acute complications or as chronic transfusion therapy (CTT) to prevent severe manifestations. The objectives of this study were to describe blood utilization and adverse events (AEs) associated with RBCs in the Brazilian SCD population and compare characteristics of patients treated or not with CTT. STUDY DESIGN AND METHODS A SCD cohort was established at six Brazilian centers. Medical and blood bank records were abstracted for clinical and transfusion history. Two controls not treated with CTT matched on center, SCD genotype, sex, and age were selected for each CTT case within the cohort to compare characteristics between the two groups. RESULTS Most of the 2794-member cohort had received a transfusion (75.0% of children and 89.2% of adults) with 29.2% of patients receiving transfusion in the prior year. There were 170 (10.6%) children and 115 (9.2%) adults treated with CTT. Children not treated with CTT were more likely to have pain and acute chest hospitalizations in the prior year (25.3% vs. 11.9%, p = 0.0003; and 22.0% vs. 10.7%, p = 0.002, respectively). Both iron overload and alloimmunization were more common in CTT cases compared to controls (65.6% vs. 17.0% and 36.2% vs. 15.9%, respectively). A higher proportion of adults treated with CTT demonstrated oxygen saturation of greater than 95% compared to controls not treated (51.1% vs. 39.2%), while there was no difference in oxygenation between children treated or not. Of 4501 transfusion episodes, 28 (0.62%) AEs were reported. There was no difference in AEs associated with transfusions for acute indications versus CTT. CONCLUSION Red blood cell transfusion was common in Brazilian SCD patients, with utilization driven by CTT. Transfusion reactions were not common; however, alloimmunization and iron overload were frequent among those on CTT, highlighting the need for novel clinical strategies to mitigate these risks.
- Hb S/beta-Thalassemia in the REDS-III Brazil Sickle Cell Disease Cohort: Clinical, Laboratory and Molecular Characteristics(2020) BELISARIO, Andre R.; CARNEIRO-PROIETTI, Anna B.; SABINO, Ester Cerdeira; ARAUJO, Aderson; LOUREIRO, Paula; MAXIMO, Claudia; FLOR-PARK, Miriam V.; RODRIGUES, Daniela D. O. W.; OZAHATA, Mina Cintho; MCCLURE, Christopher; MOTA, Rosimere Afonso; MOURA, Isabel C. Gomes; CUSTER, Brian; KELLY, ShannonWe described the clinical, laboratory and molecular characteristics of individuals with Hb S (HBB: c.20A>T)/beta-thalassemia (Hb S/beta-thal) participating in the Recipient Epidemiology and Donor Evaluation Study (REDS-III) Brazil Sickle Cell Disease cohort. HBB gene sequencing was performed to genotype each beta-thal mutation. Patients were classified as Hb S/beta(0)-thal, Hb S/beta(+)-thal-severe or Hb S/beta(+)-thal based on prior literature and databases of hemoglobin (Hb) variants. Characteristics of patients with each beta-thal mutation were described and the clinical profile of patients grouped into Hb S/beta(0)-thal, Hb S/beta(+)-thal and Hb S/beta(+)-thal-severe were compared. Of the 2793 patients enrolled, 84 (3.0%) had Hb S/beta(0)-thal and 83 (3.0%) had Hb S/beta(+)-thal; 40/83 (48.2%) patients with Hb S/beta(+)-thal had mutations defined as severe. We identified 19 different beta-thal mutations, eight Hb S/beta(0)-thal, three Hb S/beta(+)-thal-severe and eight Hb S/beta(+)-thal. The most frequent beta(0) and beta(+) mutations were codon 39 (HBB: c.118C>T) and IVS-I-6 (T>C) (HBB: c.92+6T>C), respectively. Individuals with Hb S/beta(0)-thal had a similar clinical and laboratory phenotype when compared to those with Hb S/beta(+)-thal-severe. Individuals with Hb S/beta(+)-thal-severe had significantly lower total Hb and Hb A levels and higher Hb S, white blood cell (WBC) count, platelets and hemolysis markers when compared to those with Hb S/beta(+)-thal. Likewise, individuals with Hb S/beta(+)-thal-severe showed a significantly higher occurrence of hospitalizations, vaso-occlusive events (VOE), acute chest syndrome (ACS), splenic sequestration, blood utilization, and hydroxyurea (HU) therapy.
- Association of HIV infection with clinical and laboratory characteristics of sickle cell disease(2020) BELISARIO, Andre Rolim; BLATYTA, Paula F.; VIVANCO, Diana; OLIVEIRA, Claudia Di Lorenzo; CARNEIRO-PROIETTI, Anna Barbara; SABINO, Ester Cerdeira; ALMEIDA-NETO, Cesar de; LOUREIRO, Paula; MAXIMO, Claudia; MATEOS, Sheila de Oliveira Garcia; V, Miriam Flor-Park; RODRIGUES, Daniela de Oliveira Werneck; MOTA, Rosimere Afonso; GONCALEZ, Thelma T.; HOFFMANN, Thomas J.; KELLY, Shannon; CUSTER, BrianBackground Sickle cell disease (SCD) is a multisystem disorder characterized by a wide spectrum of clinical manifestations and severity. Studies investigating potential effects of co-morbid human immunodeficiency virus (HIV) and SCD have produced conflicting results, and additional investigations are needed to elucidate whether the interaction between the two disease states might impact both HIV and SCD clinical outcomes. The association of HIV infection with clinical and laboratory characteristics of patients with SCD was assessed. Methods This nested case-control study included individuals with SCD with HIV treated at six Brazilian SCD centers. Clinical and laboratory data were abstracted from medical records. HIV positive participants were compared to age, gender, center, and SCD genotype matched HIV negative participants (ratio 1:4). Individual clinical outcomes as well as a composite outcome of any SCD complication and a composite outcome of any HIV-related complication were compared between the two groups. Results Fifteen HIV positive participants were included, 12 (80%) alive and 3 (20%) deceased. Most of the HIV positive patients had HbSS (60%;n = 9), 53% (n = 8) were female, and mean age was 30 +/- 13 years. The frequency of individual SCD complications of acute chest syndrome/pneumonia, sepsis/bacteremia, pyelonephritis, ischemic stroke, hemorrhagic stroke, abnormal transcranial Doppler (TCD), and pulmonary hypertension was higher in HIV positive participants when compared to HIV negative, although analyzed individually none were statistically significant. HIV positive participants had significantly higher risk of any SCD complication and of a composite HIV-related complication compared to the HIV negative group (HR = 4.6; 95%CI 1.1-19.6;P = 0.04 and HR = 7.7; 95%CI 1.5-40.2;P = 0.02, respectively). There was a non-significant trend towards higher risk of any infections in participants with HIV positive (HR = 3.5; 95%CI 0.92-13.4;P = 0.07). Laboratory parameters levels were not significantly different in individuals with and without HIV. Conclusions In summary, our study in SCD patients shows that those with HIV have an increased risk of any SCD complication and HIV-related complications, as well as a suggestive but not significantly increased risk of infections.